The Enterprise is playing host to Federation Science Council representative DoctorJason Crandall, an irascible bureaucrat who oversaw the creation of new sensors designed to detect gateways—portals in space, which the Enterprise had previously encountered. The Enterprise is investigating the gateways when it is thrown through one, and ends up in an unknown area of space with extremely dense star formations. After trying unsuccessfully to return through the gateway, the Enterprise sets off to explore the nearby star systems, in hopes of finding the gateways' creators, and thus a way home. However, all they find are planets rendered uninhabitable through bombardment with fusion bombs, phasers and other weapons. Finally they come across a spaceship, but rather than responding to their attempts at communication, it just attacks. Armed only with lasers, its attacks are ineffective, and so it tries to ram the Enterprise and then when this is ineffective, detonates its warp core.

The Enterprise tracks a group of six similar ships, which are attacked by a seventh. The new ship destroys two of the first group but is overwhelmed by the others. The Enterprisewarps in and beams out four of the new ship's crew, then warps away out of the enemy's sensor range. The first of the rescued crew is reintegrated, but sets off a suicide device, seriously injuring NurseGarcia. The remaining rescuees are reintegrated and stunned immediately, then have their implants surgically removed. When they wake up they refuse to talk, Kirk takes them for a tour of the ship, then shows them a presentation of Spock's to show that they are not from this region of space. The aliens finally reveal themselves as the Hoshan, named Tarasek, Radzyk and Bolduc. They explain that 100 years previously when their race first started space exploration, they came across the destroyed planets and then were repeatedly attacked. They withdrew to their home system, fortified it for 50 years, and since then shoot on sight any other ship, believing it to be "The Destroyers". They also explain why they commit suicide rather than be captured - they cannot allow themselves to give away any information, for risk of the Destroyers finding their homeworld.

Kirk decides to use probes to separate the several Destroyer ships, and use the chance to abduct several of their crew. However, before he can do this, Crandall attempts a mutiny, threatening Kirk with a phaser and putting Doctor McCoy in charge, but he is stopped by a Vulcan nerve pinch from Spock. The plan goes ahead, and several Destroyer crewmembers are beamed aboard. They also attempt to detonate suicide devices, but McCoy is able to disable them. Once woken, the first "Destroyer" says his species are the Zeator, and they are fighting against the "World Killers", their name for the Hoshan. He tells a very similar story, of finding the destroyed worlds, of ships being attacked, retreat to the homeworld and then aggressively attacking any other ship they come across in hopes of wiping out the World Killers once and for all. Kirk gives translators to the Hoshan and Zeator, and sends them off in their respective ships to contact their commanders in hopes of forging a peace deal.

A while later, leaders of the Hoshan and Zeator contact Kirk, and ask him to mediate a peace agreement onboard the Enterprise. Between them the two sides bring around 60 ships, and it becomes clear that they believe the Enterprise to be the ones who destroyed all the planets. They are about to fire on the Enterprise - Kirk orders a retreat, but Crandall, believing he will never return to the Federation and feeling the only way he could get one up on Kirk was to choose the manner of his own death, attacks Sulu before he can engage the warp drive. Spock however manages to do so in time, although the Enterprise is severely damaged, unable to go faster than warp 4 and with most of the shield generators burnt out. They limp back to where the gateway was, passing by a planet they had investigated earlier which had strange life readings. This time it shows almost 1000 humanoid life forms, but before they can investigate the entire crew is beamed off the ship.

The crew find themselves in a large cavern, with most of their equipment the other side of a strange forcefield, and in a vacuum. Crandall is attacked by several crewmembers, but is saved by Kirk, who is then beamed away to face two aliens. One says the word Aragos. Kirk tries to introduce himself, but is trapped and instead signalled to name various pieces of equipment from the Enterprise. After an hour he is beamed back, with Scotty and McCoy taken in his stead. They are returned and Spock is taken along with Crandall. Spock attempts to initiate a telepathic link to the aliens, and briefly feels all 900 aliens and 400 crew connected to him through some form of organic computer. He tries again, and manages to make the transporter operator beam them back inside the forcefield, where the equipment is. Crandall is by the equipment, and Spock a way away, unable to reach it due to the vacuum.

Extragalactic ship.

Crandall, having seen how the Starfleet crew feel about him - what he perceived as malice was by them seen as trying to help but being betrayed - throws Spock a breathing mask, and as they are beamed back, Spock manages to grab a translator. He finds that he is immediately able to understand the aliens' language, as they had previously met their species back in the Milky Way. The Aragos had been on a science expedition when they too had been taken by the gate. They were attacked but managed to make it to a planet, where they found a gateway monitoring computer, but no means to access the gateway again. Kirk takes them aboard the Enterprise, and after negotiating their way through a Hoshan/Zeator blockade, return through the gateway.

The ranks of the characters in the story and the images of the characters on the cover indicate a time period of the late 2260sdecade, but the Enterprise pictured on the cover is the Enterprise-classrefit, which was not created until the 2270s.

Although the novel is ostensibly a direct sequel to TOSnovel: The Abode of Life, that previous novel was not written by Gene DeWeese, but by G. Harry Stine under the pseudonym Lee Correy. Chain of Attack makes direct reference to the gravitational anomaly gateways and the Mercanian system, and indicates the Enterprise is following up on that mission. Stine and DeWeese had backgrounds in rocket science in real-life space research, indicating they probably worked together tying the two stories together.